Related Angiitis Research Articles

All that enhances is not cancer: Cerebral amyloid angiopathy mimicking leptomeningeal enhancement in the two patients with advanced cancer (P14-13.002)

<h3>Objective:</h3> N/A <h3>Background:</h3> Cerebral amyloid angiopathy (CAA) leads to deposition of amyloid-beta-peptide in leptomeninges and cerebral blood vessels. A <i>β</i>-related angiitis (ABRA) is a severe form of CAA characterized by transmural inflammation and/or, granulomatous inflammation. We report two patients with advanced malignancy presenting with leptomeningeal enhancement (LME) concerning for leptomeningeal metastases, with biopsy demonstrating ABRA. <h3>Design/Methods:</h3> 76-year-old man presented with left facial droop, dysarthria and imbalance. MRI head showed acute infarcts in multiple vascular distributions and diffuse LME. CTA showed bilateral cervical lymphadenopathy, without evidence of vasculitis. CSF analysis demonstrated lymphocytic pleocytosis and negative flow cytometry and cytology. Cervical lymph node biopsy revealed a new diagnosis of metastatic papillary thyroid cancer. Repeat MRI brain one month later showed persistent and worsening cortical LME. Prior to surgery for the thyroid cancer, a brain biopsy was performed for staging. Pathology demonstrated fibrinoid necrosis of vessels walls and foci of thrombosis, consistent with CAA. The patient was treated with corticosteroids followed by cyclophosphamide for ABRA. 78-year-old woman with cognitive impairment and stage IV serous endometrial cancer presented after incidental findings of subarachnoid hemorrhage (SAH) with LME on MRI brain. CSF analysis was normal with negative cytology. Head CTA was negative for aneurysm or vascular malformation. A repeat MRI showed new small SAH in the right superior frontal gyrus and multiple new punctate cerebellar infarcts. Brain biopsy revealed amyloid positivity with congo red staining in cerebellar leptomeningeal vessels, consistent with CAA. She received a 5-day course of IVIG (steroids contraindicated) with plan to start immunosuppressive therapy outpatient. <h3>Results:</h3> N/A <h3>Conclusions:</h3> Our patients presented with LME in the setting of newly diagnosed malignancy, which raised concern for leptomeningeal metastases. The presence of SAH and infarcts are uncommon in leptomeningeal metastatic disease. In these cases, pathologic confirmation of CAA on brain biopsy changed the cancer-related prognosis and treatment plan. <b>Disclosure:</b> Dr. Waheed has nothing to disclose. Dr. Seyam has nothing to disclose. Dr. Thomas has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roon. The institution of Dr. Thomas has received research support from Novocure. The institution of Dr. Thomas has received research support from Spectrum Pharmaceuticals. The institution of Dr. Thomas has received research support from Ono Pharmaceuticals.

Amyloid-\u03b2 related angiitis presenting as eosinophilic meningitis: a case report

BackgroundEosinophilic meningitis is uncommon and often attributed to infectious causes.Case presentationWe describe a case of a 72-year-old man who presented with subacute onset eosinophilic meningitis, vasculitis, and intracranial hypertension with progressive and severe neurologic symptoms. Brain MRI demonstrated multifocal strokes and co-localized right temporo-parieto-occipital vasogenic edema, cortical superficial siderosis, and diffuse leptomeningeal enhancement. He ultimately underwent brain biopsy with immunohistochemical stains for amyloid-β and Congo red that were extensively positive in the blood vessel walls and in numerous diffuse and neuritic parenchymal confirming a diagnosis of amyloid-β related angiitis. He was treated with immunosuppression with clinical stabilization.ConclusionsAmyloid-β related angiitis is an underrecognized cause of eosinophilic meningitis that can present fulminantly and is typically responsive to immunosuppression. The presence of eosinophils may provide additional clues to the underlying pathophysiology of amyloid-β related angiitis.

Bridging the Gap between Neurology and Psychiatry- Psychiatric Symptoms in the course of Neurodegenerative Disorders

It is increasingly recognized that there is significant heterogeneity in phenotype and clinical trajectories in Alzheimer's disease as well as Lewy Body and Vascular dementia. Relatively common neurodegenerative disorder, Lewy Body Dementia (LBD) presents with psychiatric features. Mood disorders are common and often precede core symptoms of LBD. Patient with LBD especially early in the course of disease are at increased risk for suicide. Psychosis is one of the most debilitating symptoms of LBD as it is an independent risk factor for nursing home placements, increased caregiver distress and mortality. Visual hallucinations are the most common psychotic manifestation in LBD. Auditory, olfactory, tactile and gustatory hallucinations and delusions are less frequently found. Global cognitive deficits including attention, frontal executive dysfunction, visuospatial abnormalities, language and verbal memory were associated with the presence of psychosis in Lewy Body Dementia. Glucocerebrosidase gene (GBA) mutations and polymorphisms found to be associated with LBD. Up to 25% of Alzheimer's disease (AD) cases do not show the typical neuropathology. Subtypes and atypical non-amnestic AD presentations have been formalized in the International Working Group (IWG) clinical diagnosis criteria. Frontal signs and symptoms are often seen in Alzheimer's disease especially in patients with early onset. In those clinical situations differential diagnosis especially distunguising between Clinical diagnosis of atypical AD has significantly been improved by the availability of biomarkers, including cerebrospinal fluid levels of Aβ42, total tau and phosphorylated tau181. MRI volumetric estimation of hippocampal and medial temporal atrophy, and amyloid brain PET imaging. We will review atypical forms of AD from these varied perspectives to help improve diagnostic confidence among clinicians. Cerebral amyloid angiopathy (CAA) is a highly prevalent pathologic finding in the elderly contributing to cognitive loss, neuropsychiatric symptoms and morbidity. It is characterized by predominantly vascular deposition of beta amyloid protein Its prevalence varies across different populations. Initially conceptualized as vascular dementia syndrome CAA was proved to overlap with AD pathology and is thought to affect over 80% of AD patients. Lobar intracerebral hemorrhage and infarction are the well-known striking clinical manifestations, but CAA has multiple other clinical phenotypes: Inflammatory disease in the form of vasculitis known as amyloid beta related angiitis (ABRA) and inflammatory leukoencephalopathy, also known as CAA related inflammation (CAA-RI). Due to multiple clinical phenotypes CAA remains clinically underdiagnosed and underreported especially in elderly with dementia and other psychiatric symptoms. The underlying pathophysiological mechanism for the spectrum of CAA will be discussed.

BRIDGING THE GAP BETWEEN NEUROLOGY AND PSYCHIATRY- PSYCHIATRIC SYMPTOMS IN THE COURSE OF NEURODEGENERATIVE DISORDERS

It is increasingly recognized that there is significant heterogeneity in phenotype and clinical trajectories in Alzheimer's disease as well as Lewy Body and Vascular dementia. Relatively common neurodegenerative disorder, Lewy Body Dementia (LBD) presents with psychiatric features. Mood disorders are common and often precede core symptoms of LBD. Patient with LBD especially early in the course of disease are at increased risk for suicide. Psychosis is one of the most debilitating symptoms of LBD as it is an independent risk factor for nursing home placements, increased caregiver distress and mortality. Visual hallucinations are the most common psychotic manifestation in LBD. Auditory, olfactory, tactile and gustatory hallucinations and delusions are less frequently found. Global cognitive deficits including attention, frontal executive dysfunction, visuospatial abnormalities, language and verbal memory were associated with the presence of psychosis in Lewy Body Dementia. Glucocerebrosidase gene (GBA) mutations and polymorphisms found to be associated with LBD. Up to 25% of Alzheimer's disease (AD) cases do not show the typical neuropathology. Subtypes and atypical non-amnestic AD presentations have been formalized in the International Working Group (IWG) clinical diagnosis criteria. Frontal signs and symptoms are often seen in Alzheimer's disease especially in patients with early onset. In those clinical situations differential diagnosis especially distunguising between Clinical diagnosis of atypical AD has significantly been improved by the availability of biomarkers, including cerebrospinal fluid levels of Aβ42, total tau and phosphorylated tau181. MRI volumetric estimation of hippocampal and medial temporal atrophy, and amyloid brain PET imaging. We will review atypical forms of AD from these varied perspectives to help improve diagnostic confidence among clinicians. Cerebral amyloid angiopathy (CAA) is a highly prevalent pathologic finding in the elderly contributing to cognitive loss, neuropsychiatric symptoms and morbidity. It is characterized by predominantly vascular deposition of beta amyloid protein Its prevalence varies across different populations. Initially conceptualized as vascular dementia syndrome CAA was proved to overlap with AD pathology and is thought to affect over 80% of AD patients. Lobar intracerebral hemorrhage and infarction are the well-known striking clinical manifestations, but CAA has multiple other clinical phenotypes: Inflammatory disease in the form of vasculitis known as amyloid beta related angiitis (ABRA) and inflammatory leukoencephalopathy, also known as CAA related inflammation (CAA-RI). Due to multiple clinical phenotypes CAA remains clinically underdiagnosed and underreported especially in elderly with dementia and other psychiatric symptoms. The underlying pathophysiological mechanism for the spectrum of CAA will be discussed

Abstract TP204: Large-Artery Infarction in Primary Angiitis of the Central Nervous System

Introduction: Primary angiitis of central nervous system (PACNS) typically manifests with accumulating small-sized ischemic strokes and white-matter changes. Large-artery infarcts (LA-PACNS) have been observed, however it is unclear whether LA-PACNS is a unique subtype. Methods: We compared the clinical/imaging phenotype, predictors, treatment response and prognosis of LA-PACNS and small-vessel PACNS (SV-PACNS) from a cohort of 51 cases meeting published criteria for PACNS (Ann Neurol. 2016;79:882-94) who were managed at our hospital from 1993-2015. Results: Overall mean age 51±15 years; 72% men. Six patients (12%, 95% CI: 3%-21%; mean age 55±13 years; 67% men) had LA-PACNS; 4 (67%) presented with discrete stroke syndromes versus 49% in SV-PACNS. The frequency of headache, encephalopathy, seizure and focal deficits were not significantly different however LA-PACNS had more hypertension. CSF, performed in all patients, showed inflammatory changes in 63% SV-PACNS versus 33% LA-PACNS (p=0.4). Brain biopsy was performed in 5 LA-PACNS and 32 SV-PACNS. In LA-PACNS, one had granulomatous angiitis (GACNS), one had amyloid-beta related angiitis (ABRA), and 3 had negative results. In SV-PACNS, 18 (56%) showed abnormal results including lymphocytic/chronic (12), GACNS (5), ABRA (1). There were no significant differences in the frequency of angiographic abnormalities (67% vs 53%), arteriopathy severity score (10±10 vs 8±13), or arterial segment involved. There were no significant differences in the degree of white matter change, microbleeds, or contrast enhancement on MRI however LA-PACNS had more FLAIR dot sign indicating slow flow and collateralization in leptomeningeal arteries (40% vs 5%, p=0.05). Except for two patients with SV-PACNS, all were treated with steroids; 23 SV-PACNS and all LA-PACNS also received cyclophosphamide. The interval from onset to diagnosis was shorter in LA-PACNS (42 vs 110 days) and follow-up duration was similar (5.4±7.5 years vs. 5.9±6.3 years). Mortality (33% LA-PACNS vs 16% SV-PACNS) and full remission (50% vs 62%) were not significantly different. Conclusions: In our relatively large cohort of PACNS, LA-PACNS and SV-PACNS showed similar clinical, imaging, angiographic features and outcome.

Cerebral amyloid angiopathy associated with inflammation: A systematic review of clinical and imaging features and outcome.

Background Cerebral amyloid angiopathy associated with inflammation is an increasingly recognized condition, characterized by an inflammatory response to the vascular deposits of β-amyloid within the brain that are the hallmark of cerebral amyloid angiopathy. Two main patterns of this inflammatory response have been identified to date: one involving a perivascular inflammatory cell infiltrate (cerebral amyloid angiopathy-related inflammation); the other a transmural vasculitic process (A-beta related angiitis). Unlike cerebral amyloid angiopathy itself, which predisposes to intracerebral hemorrhage and has no known treatment, cerebral amyloid angiopathy associated with inflammation typically presents in diverse ways and diagnosis may be challenging and delayed. Aims We sought to summarize the clinical features, imaging appearances and available data on outcome and treatment responses, using information derived from a systematic review of pathologically proven cases of cerebral amyloid angiopathy associated with inflammation. Summary of review We identified 213 distinct pathologically proven cases of cerebral amyloid angiopathy-related inflammation/A-beta related angiitis, from 104 publications. The clinical presentation, imaging features, pathology, treatment, and outcomes of cerebral amyloid angiopathy associated with inflammation are described. Conclusions Cerebral amyloid angiopathy associated with inflammation is an important and increasingly recognized clinical condition, which affects the older patient population and presents most commonly with cognitive decline, seizures, and headaches. Future research is required to develop and validate diagnostic criteria and determine optimum treatment strategies.

Amyloid-Beta Related Angiitis of the Central Nervous System: Case Report and Topic Review

Amyloid-beta related angiitis (ABRA) of the central nervous system (CNS) is a rare disorder with overlapping features of primary angiitis of the CNS and cerebral amyloid angiopathy. We evaluated a 74-year-old man with intermittent left sided weakness and MRI findings of leptomeningeal enhancement, vasogenic edema, and subcortical white matter disease proven to have ABRA. We discuss clinicopathological features and review the topic of ABRA.

Intracranial Imaging of Uncommon Diseases Is More Frequently Reported in Clinical Publications Than in Radiology Publications

Descriptions of uncommon diseases with intracranial imaging abnormalities are often difficult to find in the radiology literature. We hypothesized that reported imaging findings of such conditions in the recent literature were more frequent in clinical compared with radiology journals. PubMed searches from December 1, 2007 to December 1, 2012 were performed for 5 uncommon CNS diseases with intracranial imaging manifestations: 1) Susac syndrome; 2) amyloid β-related angiitis; 3) Parry-Romberg syndrome/en coup de sabre; 4) transient lesion of the splenium of the corpus callosum; and 5) reversible cerebral vasoconstriction syndrome. Articles were classified as a case report, case series, or original research. Journals were categorized as radiology or clinical. The 1- and 5-year Impact Factors of the journals were recorded. Two hundred two articles were identified for the 5 diseases, including 151 (74%) case reports, 26 case series (13%), and 25 original research articles (13%); 179 (89%) were published in nonradiology journals, compared with 23 (11%) in radiology journals. There was no significant difference between the mean 1- and 5-year Impact Factors of the radiology and clinical journals. Recent reports of the selected uncommon diseases with intracranial manifestations are more frequent in clinical journals when compared with dedicated radiology publications. Most publications are case reports. Radiologists should review both radiology and clinical journals when reviewing imaging features of uncommon diseases affecting the brain. Lack of reporting on such disease in the radiology literature may have significant practice, educational, and research implications for the radiology community.

Teaching Neuro Images : Treatment-resistant rapidly progressive amyloid β–related angiitis

A 76-year-old woman presented with 1 month of progressive aphasia, headache, and subsequent right hemiparesis. Initial brain MRI showed a punctate infarct (figure 1, A and C). Susceptibility-weighted imaging was unremarkable. A repeat study 16 days later demonstrated bihemispheric infarcts with multifocal attenuation of intracranial vessels on magnetic resonance angiography (figure 1, B and D). CSF showed a lymphocytic pleocytosis (101 leukocytes/µL) and elevated protein (480 mg/dL). Brain biopsy showed granulomatous angiitis with amyloid deposition and fibrinoid necrosis surrounded by inflammatory cells (figure 2). She rapidly deteriorated on immunosuppression with high-dose IV steroids and has not improved despite a combination of oral steroids and monthly cyclophosphamide.

A Case of Amyloid-β-Related Angiitis: Histology, CSF-Findings and Treatment

Amyloid- β -related angiitis (ABRA) is characterized by vasculitis and accumulation of amyloid- β in vessel walls. In this case report we describe findings of cranial MRI, brain biopsy and cerebrospinal fluid in a patient with Amyloid- β -related angiitis. The cranial MRI displayed extensive multifocal white matter lesion and brain biopsy revealed amyloid angiopathy as well as granulomatous angiitis. In the cerebrospinal fluid our patient showed normal cell count, slightly elevated protein and intrathecal immunoglobulin synthesis which recovered during steroid therapy. We illustrate that detailed CSF analysis including tests for intrathecal immunoglobulin synthesis is very useful in monitoring the efficacy of therapy and disease activity in ABRA since cranial MRI and histology are not suitable for this purpose. In addition we propose that CSF findings may be very helpful in diagnosing ABRA and starting early immunosuppressive therapy. doi: http://dx.doi.org/10.4021/jnr123w

A Case of Amyloid-β-Related Angiitis: Histology, CSF-Findings and Treatment

Amyloid- β -related angiitis (ABRA) is characterized by vasculitis and accumulation of amyloid- β in vessel walls. In this case report we describe findings of cranial MRI, brain biopsy and cerebrospinal fluid in a patient with Amyloid- β -related angiitis. The cranial MRI displayed extensive multifocal white matter lesion and brain biopsy revealed amyloid angiopathy as well as granulomatous angiitis. In the cerebrospinal fluid our patient showed normal cell count, slightly elevated protein and intrathecal immunoglobulin synthesis which recovered during steroid therapy. We illustrate that detailed CSF analysis including tests for intrathecal immunoglobulin synthesis is very useful in monitoring the efficacy of therapy and disease activity in ABRA since cranial MRI and histology are not suitable for this purpose. In addition we propose that CSF findings may be very helpful in diagnosing ABRA and starting early immunosuppressive therapy. J Neurol Res. 2012;2(4):168-171 doi: https://doi.org/10.4021/jnr123w

Amyloid β-related Angiitis of the Central Nervous System: Report of 3 Cases

Amyloid-β (Aβ) related angiitis (ABRA) is a recently described clinicopathological entity characterized by cerebrovascular Aβ deposition and arteritis. Cerebral Aβ deposition is commonly present in cerebal amyloid angiopathy (CAA) and Alzheimer's disease (AD) but is rarely associated with inflammatory infiltration of vessel walls. Our objective is to help clarify the clinical spectrum, radiographic findings, response to treatment, and outcomes of ABRA. The neuropathological relationship between ABRA, cerebral amyloid angiopathy, and Alzheimer's disease is discussed. We present three cases of ABRA managed at a tertiary care centre. All three patients presented with seizures and cognitive dysfunction; one had multifocal neurologic findings. Brain biopsies revealed inflammatory arteritis with Aβ deposits in the vessel walls. All were treated with steroids and cyclophosphamide. Two had favorable outcomes and one stabilized but with severe residual neurologic disability. ABRA is an unusual but likely under-recognized and potentially treatable disorder. As in other reported cases, our findings suggest that many patients respond favorably to immunosuppressive therapy. We believe that all biopsy specimens consistent with primary angiitis of the central nervous system (CNS) should be further examined for vascular Aβ deposition.

Inflammation Complicates an ‘Age-Related’ Cerebral Microangiopathy

Inflammation Complicates an ‘Age-Related’ Cerebral Microangiopathy

MRI in amyloid β–related brain angiitis

A 52-year-old man presented with complex partial seizures. Fluid-attenuated inversion recovery MRI showed multifocal subcortical and cortical edema, predominantly in the left temporal lobe (figure, A). T2-weighted and gradient echo images showed multiple cortical microbleeds (figure, B–D). Right frontal brain biopsy revealed amyloid β–related angiitis showing leptomeningeal and cortical blood vessels with vascular β–amyloid deposition and perivascular/intramural inflammatory …

A -related angiitis: primary angiitis of the central nervous system associated with cerebral amyloid angiopathy

Idiopathic or primary angiitis of the CNS (PACNS) and cerebral amyloid angiopathy (CAA) are unusual vasculopathies generally regarded as unrelated disorders. A few case reports have, however, described granulomatous angiitis in patients with sporadic, amyloid beta peptide (Abeta)-related CAA. Here we describe the clinical, neuroradiological and neuropathological features of nine patients with Abeta-related angiitis (ABRA). Combining these with the individual case reports drawn from the literature has allowed us to define ABRA as a clinical entity and to compare its features with those of PACNS. The mean age of presentation of ABRA (67 years) is higher than that of PACNS but lower than that of sporadic non-inflammatory Abeta-related CAA. Alterations in mental status (59%), headaches (35%), seizures and focal neurological deficits (24%) are common. Hallucinations are a presenting manifestation in 12% of cases. Most patients have white matter hyperintensities on MRI but these are of similar appearance to those in PACNS. Cerebrospinal fluid usually shows modest elevation of protein and pleocytosis. Neuropathology reveals angiodestructive inflammation, often granulomatous, and meningeal lymphocytosis. Abeta is consistently present in abundance in affected blood vessels but usually scanty within the parenchyma of the cerebral cortex. However, the cortex includes numerous activated microglia, occasionally in a plaque-like distribution and containing cytoplasmic Abeta. The cerebral white matter shows patchy gliosis and rarefaction, in some cases marked. Our findings (i) help to dissect one separate clinicopathological entity from what is likely to be a spectrum of primary angiitides of the CNS; (ii) have important therapeutic implications for one category of patients with amyloid-related vasculopathy; and (iii) may provide valuable insights into the development of amyloid-associated inflammation, of relevance not only to ABRA but also to Abeta-immunization-related encephalitis and to Alzheimer's disease.